4-(4-{[2-(4-chlorophenyl)phenyl]methyl}piperazin-1-yl)-N-(4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzenesulfonyl)benzamide

• ChemBase ID: 72452
• Molecular Formular: C42H45ClN6O5S2
• Molecular Mass: 813.4269
• Monoisotopic Mass: 812.25813825
• SMILES: c1cc(ccc1C(=O)NS(=O)(=O)c1ccc(c(c1)[N+](=O)[O-])N[C@@H](CSc1ccccc1)CCN(C)C)N1CCN(CC1)Cc1c(cccc1)c1ccc(cc1)Cl
• Canonical SMILES: CN(CC[C@@H](Nc1ccc(cc1[N+](=O)[O-])S(=O)(=O)NC(=O)c1ccc(cc1)N1CCN(CC1)Cc1ccccc1c1ccc(cc1)Cl)CSc1ccccc1)C
• InChI: InChI=1S/C42H45ClN6O5S2/c1-46(2)23-22-35(30-55-37-9-4-3-5-10-37)44-40-21-20-38(28-41(40)49(51)52)56(53,54)45-42(50)32-14-18-36(19-15-32)48-26-24-47(25-27-48)29-33-8-6-7-11-39(33)31-12-16-34(43)17-13-31/h3-21,28,35,44H,22-27,29-30H2,1-2H3,(H,45,50)/t35-/m1/s1
• InChIKey: HPLNQCPCUACXLM-PGUFJCEWSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-(4-{[2-(4-chlorophenyl)phenyl]methyl}piperazin-1-yl)-N-(4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzenesulfonyl)benzamide
• IUPAC Traditional name: 4-(4-{[2-(4-chlorophenyl)phenyl]methyl}piperazin-1-yl)-N-(4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzenesulfonyl)benzamide
• Synonyms: ABT-737; 4-[4-[(4’-Chloro[1,1’-biphenyl]-2-yl)methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl]amino]-3-nitrophenyl]sulfonyl]benzamide; ABT 737

Database IDs

• CAS Number: 852808-04-9
• PubChem SID: 162037377
• PubChem CID: 11228183

CALCULATED PROPERTIES

• Acid pKa: 4.2773795
• H Acceptors: 9
• H Donor: 2
• LogD (pH = 5.5): 4.559849
• LogD (pH = 7.4): 6.3591967
• Log P: 7.4634604
• Molar Refractivity: 230.6089 cm^3
• Polarizability: 88.638306 Å^3
• Polar Surface Area: 130.81 Å^2
• Rotatable Bonds: 15
• Lipinski's Rule of Five: false

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol
• Apperance: Yellow Solid
• Melting Point: 152-154°C

Safety Information

• Storage Condition: -20°C; -20°C Freezer

Pharmacology Properties

• Target: Bcl-2

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1002

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• Fluorescence polarization assays: Binding affinity of GST-Bcl-2 family proteins to the FITC-conjugated BH3 domain of Bim (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR) is determined. Briefly, 100 nM of GST-Bcl-2 family fusion proteins are incubated with serial dilutions of ABT-737 in PBS for 2 min. Then, 20 nM of FITC-Bim BH3 peptide (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR) is added. Fluorescence polarization is measured using an Analyst TM AD Assay Detection System after 10 min using the 96-well black plate. Then IC50 are determined.
• Protocol: Cell Assay ^[4]
• Cell Lines: SCLC cell lines NCI-H889, NCI-H1963, NCI-H1417, NCI-H146, NCI-187, DMS79, NCI-1048, NCI-H82, NCI-H196, H69AR, and DMS114
• Concentrations: 0.001-10 μM
• Incubation Time: 48 hours
• Methods:

  SCLC cells are treated for 48 hours in 96-well tissue culture plates in a total volume of 100 μL tissue culture medium supplemented with 10% human serum. Viable cells are determined using the MTS assay.

• Protocol: Animal Study ^[1]
• Animal Models: Scid mice injected with Luc-expressing FD/ΔRaf-1:ER cells
• Formulation: 1 g/mL stock solution of ABT-737 in DMSO is added to a mixture of 30% propylene glycol, 5% Tween 80, 65% D5W (5% dextrose in water) (pH 4?5; final concentration of DMSO ≤ 1%)
• Doses: 20 and 30 mg/kg
• Administration: For intraperitoneal (i.p.) every day

References

• References: [1] Konopleva M, et al. Cancer Cell, 2006, 10(5), 375-388.
• References: [2] van Delft MF,et al. Cancer Cell, 2006, 10(5), 389-399.
• References: [3] Del Gaizo Moore V, et al. J Clin Invest, 2007, 117(1), 112-121.
• References: [4] Tahir SK, et al. Cancer Res, 2007, 67(3), 1176-1183.
• References: [5] Ishitsuka K, et al. Cancer Lett, 2012, 317(2), 218-225.
• References: [6] Hikita H, et al. Hepatology. 2010, 52(4), 1310-21.
• References: [7] Whitecross KF, et al, Blood, 2009, 113(9), 1982-1991.

Toronto Research Chemicals - A112550

A selective inhibitor of BCL-2, in small cell lung cancer. ABT-737 induced dramatic regressions in tumors derived from some SCLC cell lines.

REFERENCES

• Tahir SK, et al. Cancer Res, 2007, 67(3), 1176-1183.
• Ishitsuka K, et al. Cancer Lett, 2012, 317(2), 218-225.
• Hikita H, et al. Hepatology. 2010, 52(4), 1310-21.
• Whitecross KF, et al, Blood, 2009, 113(9), 1982-1991.
• Konopleva M, et al. Cancer Cell, 2006, 10(5), 375-388.
• van Delft MF,et al. Cancer Cell, 2006, 10(5), 389-399.
• Del Gaizo Moore V, et al. J Clin Invest, 2007, 117(1), 112-121.
• Ikegaki, N., et al.: Cancer Res., 54, 6 (1994)
• Kaiser, U., et al.: Lung Cancer, 15, 31 (1994)
• Rudin, C., et al.: J. Clin. Oncol., 22, 1110 ( 2004), Konopleva, M., et al.: Cancer Cell, 10, 375 (1994)
• Trudel, S., et al.: Clin. Cancer Res., 13, 621 (2007)